Electroplated nickel silver
"On reading," by Simon Wain-Hobson, is a weekly discussion of scientific papers and news articles around gain of function research in virology.
Since January 2024, Dr. Wain-Hobson has written weekly essays for Biosafety Now discussing risky research in virology. You can read his entire series here.
Health warning: some word plays might cause fever.
The introduction ends with, our focus will be to make the case for the scientific and moral value of GOF-type research provided that it can be conducted safely. First, methinks ethical is the word. Second, many essays have exposed the vacuity of the original claims of Drs. Fouchier & Kawaoka.
For example, the same mutations identified by the Fouchier group, when introduced into a different H5N1 background, yielded a different HA phenotype. This implies that insights gained from one set of mutations in one strain are unlikely to be generalizable to other strains given sequence differences. This was pointed out at the time, but facts didn’t stop 22 flu virologists led by Drs. Fouchier & Kawaoka from calling for GOF research on the bird H7N9 virus a few years later.
The question remains, how does society at large, and the scientific community and regulatory agencies in particular, weigh the risks and benefits? The difficulty lies largely in trying to apply quantitative risk assessment measures to the problem. The benefits of all biological research, not just GOF research, often do not make themselves apparent until years or even decades after the experiments are performed. On the other hand, the risks, even when theoretical, manifest themselves in the present when the experimentation is done. There is much to unload.
• It’s not difficult to weigh the risks and benefits, for the latter were close to zero while in the risk column there is anything from 1 to 20+ million deaths. Where’s the problem? The chill from the NIH explains why the easiest possible risk/benefit analysis – zero vs anything from 1 to 20+ million lives – has never been called.
• The benefits of research may need a little time to be perceived. Decades? Possible, but rare. Behind this ‘you never know’ argument the idea is to continue risky research. However, what if, two or three decades later, no tangible benefits emerge, what then? Nothing is said because continuing the work is the gig. Surreal.
• When writing grant proposals authors put a premium on saying that their work will solve this or that problem if funded. This is repeated in the abstract and discussion of their papers once the work is completed some 2-3 years on from being awarded the grant. Not decades down the line. Science fiction.
In our view the most important consequence of the GOF debate is that it brought renewed attention to biosafety protocols and ushered innovation in answering the relevant biological questions with greater safety. No, making novel human viruses was the most important insanity, apologies, consequence. The biosafety questions should have been addressed before such work was done.
In the section The Moral Dimension we learn that The first concern is the potential for misuse of any information or product generated by GOF research by bad actors. They go on to add that the unredacted publication of the Fouchier and Kawaoka papers was allowed by the NIH’s NSABB committee after judging that the risk of misuse was outweighed by the potential benefits. The NSABB committee was full of academics who had very little biosecurity experience. Publication finally ensued after pressure came from the NIH high table, which was in favor of GOF 2.0 virology (Chilled virology).
As we have seen the NIH still hasn’t addressed the Dual Use issue associated with the phenomenal firepower of molecular genetics (Virus Research of Concern).
Such misuse of GOF research is certainly possible. But one serious problem in an ethical evaluation of possible misuse is the difficulty of estimating the likelihood and potential impact of misuse. One can imagine numerous different scenarios involving everyone from major state actors and non-state terrorist organizations to freelance mischief-makers working in a home basement lab. There is no way to quantify over so many possibilities, let alone to assay systematically the effects that such a diverse array of actors might achieve.
So apart from having from 1 to 20+ million deaths in the risk column, they haven’t the slightest idea how to quantify over so many possibilities. Yet Drs. Casadevall and Imperiale were on the NSABB committee that approved unredacted publication of the Fouchier and Kawaoka GOF 2.0 studies after judging that the risk of misuse was outweighed by the potential benefits. They ‘knew’ back then. But now, it’s oh so complex. Go figure… although wait for the showdown coming up.
Then four remarkable sentences are unleashed. Of course one could imagine a nation like North Korea aspiring to a bioweapon capability, and as they have demonstrated with their successes in offensive cyber operations, ballistic missiles, and nuclear weapons, there is no lack of technical talent in North Korea. For all of these reasons, the risk of publication of GOF research related to misuse of biotechnology seems to have receded from the forefront of concern. In addition, the scientific publishing community is much more aware of these issues, and many journals have instituted internal reviews for papers that include DURC. The more prominent worry today is about accidently unleashing the very kind of global pandemic that one was seeking to prevent.
Sentence 1: With Prudence gone, luckily Lucidity was somewhere.
Sentence 2: How can this conclusion follow on from the previous pertinent sentence? Anyway, you got it wrong. Seven years on from the publication of this paper, the misuse of possible GOF research is in the minds of the FBI and the CIA.
Sentence 3: Publishers come in at the very end. Why should they have any say in the matter? Do they mean to shunt the final decision over US taxpayer funded research to the Nature editorial room in London. Really?
Anyway, increasingly life science papers are published on preprint servers, so the information is out before journals can do anything. This is just a little flattery of stalwart defenders of GOF 2.0 research on viruses.
Earlier on in the paper we learnt something about the publication of the resurrected Spanish flu virus Although the NSABB voted to recommend publication, the editor of Science made it clear that the journal would have published the article irrespective of the NSABB vote unless the paper was classified. The Science editor thinks he and his staff know better than a NIH run committee full of infectious disease academics of professorial rank.
Excuse me but On reading begs to differ. Scientific journals are clearing houses for state and philanthropic funded research. 1) They turn to scientists to review manuscript precisely because they don’t know better than academics. 2) They shouldn’t be allowed anywhere near policy decisions concerning GOF research.
Sounds like a free for all. For a postmortem on this controversy see 1918 and all that.
Sentence 4: Exactly. We’ve had our Chernobyl moment with the 1977 flu pandemic while the jury is out concerning the origin of the COVID-19 virus.
The authors move on to discussing the probability of a lab leak. …one source claims a 0.01% to 0.1% probability per year of research in a BSL-3 lab of an accidental release of highly transmissible influenza virus that would kill between 200,000 and 16 million people. If this is a reliable estimate, that’s a scary prospect. On the other hand, one of the authors of the original H5N1 studies has calculated the risks to be much, much lower.
They admit that the findings of the first study are scary, if reliable. At no moment do they question the work or point out a flaw. They counter it with another study that calculated the risks to be astronomically lower - actually a paper by GOF 2.0 champion Dr. Fouchier.
Now Van Noorden showed back in 2013 that scientists underestimate risk and overestimate the benefits of their work.
Perhaps an amusing illustration not from that study? At the Royal Society meeting on April 3, 2012 organized by Sir John Skehel and On reading, Ron Fouchier said if in the unlucky incident of an individual exposure, the public will not be exposed. Gosh, what does he know that we don’t?
Now juxtapose this with a remark from Edward John Smith, Captain of the Titanic reported in The Washington Times on April 16, 1912, almost a hundred years ago to the day, …the Olympic is unsinkable, and the Titanic will be the same when she is put in commission.
Given these biases and inherent conflicts of interest, proponents of risky research or their institutions shouldn’t get to make the calls on risk/benefit assessments. Binning Fouchier’s study, there is nothing to counter the numbers from the study that if a reliable estimate, that’s a scary prospect.
Then another cluster of sentences hit. First up is There are still deeper problems with a cost-benefit approach to assess the ethics of GOF research. This implies that the ethics of GOF research depends on a number emerging from a risk-benefit analysis. Simple issues like deliberately making the world a more dangerous place, or first do no harm, are not addressed.
Proponents of GOF research argue that it can play a crucial role in preventing or lessening the effects of a global pandemic by enabling mitigation factors such as early detection and the rapid development of vaccines. Bird flu GOF 2.0 research hasn’t helped make vaccines. Yet as we’ve seen before, when bereft of ideas use the development of vaccines claim (1918 and all that). Akin to the get-out-of-jail card in Monopoly.
One obvious additional risk, then, is the risk of a global pandemic that might have been prevented or mitigated by continuing GOF research. That risk is even more difficult to quantify than the risk of pandemic through accidental release. Still, it must be part of a comprehensive analysis, and since its major consequence, e.g., a global pandemic, is just as severe as a pandemic caused by accidental release, such a scenario would loom just as large as the accidental release scenario in a thorough cost-benefit analysis. This Gordian knot is quickly resolved when you realize that there are no benefits to the work of Drs. Fouchier and Kawaoka. Only risk (Virus research of concern). If you insist otherwise, despite the data available, that’s your knot.
Next up is knowledge brings increased ability to promote the good and to mitigate suffering. New knowledge can always be used for evil ends, but how we use that knowledge is a moral choice, and if we don’t have that knowledge in the first place, then we cannot use it for the good. Here there is recognition of the dual use nature of knowledge, yet it includes the paralyzing conclusion that we need knowledge to do good - even if it needs decades to be perceived - even if it can always be used for evil ends. This brings us back to risk/benefit analyses which they have knotted up.
New knowledge can always be used for evil ends. This is in conflict with the remark of present author Mike Imperiale who said in 2021 that there is only one “really tiny part” of virology that needs looking at. Has he moved on? No, it is more obfuscation designed to confuse people allowing the work to proceed piano, piano.
Drs. Casadevall and Imperiale have featured in numerous essays all published after this 2018 publication. Every time they push back on anything that could cast a shadow on GOF 2.0 virology (Deconstructing the portrait, Going places, Flights from reason, Perilous posturing).
As more tiring wordplays ensue let’s jump to the last paragraph. How otherwise should we proceed? This is not a hard question. Think about both risks and benefits, take obvious precautions, and then make the prudent choice. With enhanced biosafety protocols and improvements in the public health response, we should not ban GOF research but monitor it. The relevant research communities should insist upon stringent norms for the conduct of the research and in safety protocols. Provided that these conditions are met, there is no obvious reason why GOF type of experimentation should not go forward.
There you have it. The work must go on, the solution simple - take their word for it. There is nothing about morals. Risks and benefits? Irrelevant, for they have decided there is no obvious reason why GOF… should not go forward. Sorry gents. What are your reasons, where are your supporting risk benefit analyses, especially as you have made a point of showing how complex and difficult they are to make? Nowhere.
To retain influence some people deliberately complicate things to confuse the listener. Then they come back with something like ‘fortunately we can get you out of this mess, trust us.’ Unfortunately, we no longer do.
Conclusion
The only metal around is some tarnished electroplated nickel silver.
Aside 1
On reading cannot help thinking of the first stanza of WB Yeats WWI poem, the Second coming. Emphasis in bold is worth mulling over.
Turning and turning in the widening gyre
The falcon cannot hear the falconer;
Things fall apart; the centre cannot hold;
Mere anarchy is loosed upon the world,
The blood-dimmed tide is loosed, and everywhere
The ceremony of innocence is drowned;
The best lack all conviction, while the worst
Are full of passionate intensity.
Aside 2
By way of a series of articles in The Chicago Tribune more than 30 years ago, Pulitzer Prize winner John Crewdson exposed Dr. Robert Gallo and his false claim to have co-isolated the AIDS virus. He said Gallo told complicated lies that needed time to expose them by which time he’d uttered more. This can be found in his book Science Fictions: A Scientific Mystery, a Massive Cover-Up, and the Dark Legacy of Robert Gallo (2002) which is still available on Amazon.
Steve Bannon’s talk of flooding the zone is a more brazen and contemporary version.
Aside 3
William Faulkner has a glorious line in his book, The Town (1957).
If it aint complicated it dont matter whether it works or not because if it aint complicated up enough it aint right. So even if it works, dont believe it.
Aside 4
When contacted by email, Salvador Dali said he was sorely tempted, but in the end declined to comment.
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